PI-03: THE EFFECT OF HYDROXYUREA IN THE GUT MICROBIOME OF ANGOLAN CHILDREN WITH SICKLE CELL DISEASE
Authors: DELGADINHO M., GINETE C., FERNANDES C., SANTOS B., VASOONCELOS J., BRITO M.
Journal: HemaSphere (2022)

Purpose: Sickle cell disease (SCD) is one of the most prevalent genetic disorders, affecting around 20 to 25 million individuals throughout the world. In Sub-Saharan Africa, where it is more prevalent, it can contribute up to 80% of under-5 mortality. Clinical manifestations of SCD are very heterogeneous and the intestinal microbiome has recently been reported to be crucial in the modulation of inflammation, cell adhesion and induction of aged neutrophils, which are key interveners of recurrent vaso-occlusive crises. Since gut bacteria can regulate aged neutrophils, defects in either the integrity of the intestinal walls or a chronic disequilibrium of the microbiota are very likely to emerge in SCD patients. Moreover, it has been suggested that Hydroxyurea (HU), the most common treatment for SCD, shows a multimodal action and may reduce microbiome dysbiosis and aged neutrophils. In this context, we aimed to understand how SCD and HU treatment modulates the microbiome and if these changes could be related with disease severity. Materials and methods: In order to characterize the gut microbiome of an SCD pediatric population, which consisted of Angolan children before and after 6 months of continuous HU treatment, a total of 66 stool samples were collected in tubes with a preservative solution. Then, the metagenomic DNA was extracted, quantified and the bacterial 16SRNA gene for the V3-V4 regions was sequenced by NGS. Microbiome taxonomic profiling analysis was performed with the EzBioCloud pipeline and differences between the two groups were assessed with the Statistical Analysis of Metagenomic Profiles (STAMP) software, using Welch’s t-test. Results: Significant associations were observed in alpha-diversity between the two groups, with higher values for the children naïve for HU in several parameters, namely in OTU species count (p<0.001), phylogenetic diversity (p=0.004) and microbial richness (p<0.001), which was calculated by the ACE, Chao1 and Jackknife indices. We also noticed that children after HU treatment had higher proportions of some bacteria associated with health, including Blautia luti, Roseburia inulinivorans, Lactobacillus rogosae and Faecalibacterium, when compared to the beginning of the study. Additionally, the proportion of Firmicutes phylum was significantly lower before HU. Conclusion: This was the first study to report gut microbiome changes before and after HU treatment in SCD children. Overall, our findings provide a rationale for further research about gut microbiota dysbiosis in this population. Determining the effect of specific bacteria will give evidence for the correction of microbiota composition and supplementation with beneficial strains in order to reduce gut microbiota-driven inflammation, which could ultimately mitigate disease severity. This work was supported by FCT/Aga Khan (project n°330842553) and FCT/MCTES (UIDB/05608/2020 and UIDP/05608/2020) –H&TRC. The authors do not declare any conflict of interest